No abstract

Estrogen (E2)-responsive peripheral tissues, such as skeletal muscle, may suffer from hormone deficiency after menopause potentially contributing to the aging of muscle. However, recently E2 was shown to be synthesized by muscle and its systemic and intramuscular hormone levels are unequal. The objective of the study was to examine the association between intramuscular steroid hormones and muscle characteristics in premenopausal women (n = 8) and in postmenopausal monozygotic twin sister pairs (n = 16 co-twins from eight pairs) discordant for the use of E2-based hormone replacement. Isometric skeletal muscle strength was assessed by measuring knee extension strength. Explosive lower body muscle power was assessed as vertical jump height. Due to sequential nature of enzymatic conversion of biologically inactive dehydroepiandrosterone (DHEA) to testosterone (T) and subsequently to E2 or dihydrotestosterone (DHT), separate linear regression models were used to estimate the association of each hormone with muscle characteristics. Intramuscular E2, T, DHT, and DHEA proved to be significant, independent predictors of strength and power explaining 59–64% of the variation in knee extension strength and 80–83% of the variation of vertical jumping height in women (P < 0.005 for all models). The models were adjusted for age, systemic E2, and total body fat mass. The statistics used took into account the lack of statistical independence of twin sisters. Furthermore, muscle cells were shown to take up and actively synthesize hormones. Present study suggests intramuscular sex steroids to associate with strength and power regulation in female muscle providing novel insight to the field of muscle aging.

Estrogen-based hormone replacement therapy (HRT) may be associated with deceleration of cellular aging. We investigated if long term HRT has effects on leucocyte (LTL) or mean and minimum skeletal muscle telomere length (SMTL) in a design that controls for genotype and childhood environment. Associations between telomeres, body composition and physical performance were also examined. 11 monozygotic twin pairs (age 57.6±1.8 years) discordant for HRT were studied. Mean duration of HRT use was 7.3±3.7 years in the user sister, while their co-twins had never used HRT. LTL was measured by qPCR and SMTLs by Southern blot. Body and muscle composition were estimated by bioimpedance and computed tomography, respectively. Physical performance was measured by jumping height and grip strength. HRT users and non-users did not differ in LTL or mean or minimum SMTL. Within-pair correlations were high in LTL (r=0.69, p=0.020) and in mean (r=0.74, p=0.014) and minimum SMTL (r=0.88, p=0.001). Body composition and performance were better in users than non-users. In analyses of individuals, LTL was associated with BMI (r 2 =0.30, p=0.030), percentage total body (r 2 =0.43, p=0.014) and thigh (r 2 =0.55, p=0.004) fat, while minimum SMTL was associated with fat-free mass (r 2 =0.27, p=0.020) and thigh muscle area (r 2 =0.42, p=0.016). We found no associations between HRT use and telomere length. Longer LTLs were associated with lower total and regional fat, while longer minimum SMTLs were associated with higher fat-free mass and greater thigh muscle area. This suggests that telomeres measured from different tissues may have different associations with measures of body composition.Keywords: estrogen, telomeres, percentage of fat, fat free mass, computed tomography, bioimpedance, twin design, post-menopausal 3 Telomeres, which are non-coding DNA sequences capping the end of eukaryotic chromosomes, are known to play an important role in genome protection. In cell cultures, telomeres have be shown to shorten after each round of cell division (Allsopp et al., 1992) until they reach a critical length and the cell loses its ability to further divide. In this respect, telomere length has been used as an indicator of both replicative history and regenerative potential. Telomere erosion can also be counterbalanced by telomerase, an enzyme able to elongate telomeric ends, such as in highly proliferating stem cells (Blasco, 2005;Bodnar et al., 1998; Oeseburg et al., 2010).Aging is known to be associated with telomere shortening in some tissues, such as blood, whereas in other tissues, such as skeletal muscle, the question is still a matter of debate (Daniali et al., 2013;Decary et al., 1997;. The in vivo biology of telomeres remains imperfectly understood and may be governed by several other regulatory factors (de Lange, 2006; Ponsot et al., 2012). Such complex interplay could partly explain why telomere length is not influenced by aging alone but also by environmental factors. For example, chronic life stress has been suggested to acc...